September 26, 2013

ORLANDO, Fla. — Patients with pulmonary hypertension and elevated galectin-3 were more likely to have a higher mortality rate at 4 years compared with patients with lower levels of the biomarker, according to data presented at the Annual Scientific Meeting of the Heart Failure Society of America.

Previous research has linked high levels of galectin-3 to increased mortality in HF. However, the association had not been studied in patients with pulmonary hypertension, Santhosh R. Mannem, MD, of Montefiore Medical Center, New York, said during a presentation.

“To our knowledge, this study shows for the first time that galectin-3 levels are significantly elevated and have strong prognostic value in [pulmonary arterial hypertension] and [HF with preserved ejection fraction-induced pulmonary hypertension],” Mannem said.

Researchers measured galectin-3 levels in patients with PAH (n=37) and HF with preserved ejection fraction-induced pulmonary hypertension (n=39; left ventricular ejection fraction ≥50%) using an ELISA kit provided by BG Medicine. The mean galectin-3 level in the entire study cohort was 29.3 ng/mL, which is significantly higher than the normal value of 17.8 ng/mL, Mannem said.

Patients were divided into tertiles based on galectin-3 levels: <20.4 ng/mL, 20.4 ng/mL to 30.2 ng/mL, and >30.2 ng/mL.

Mortality at 4 years — the primary outcome of the study — was 16% in patients with a galectin-3 level <20.4 ng/mL, 34.6% with a level of 20.4 ng/mL to 30.2 ng/mL and 48% with a level >30.2 ng/mL (P=.017). The researchers found that galectin-3 was a strong predictor of mortality based on univariate analysis (HR=2.09 per tertile; 95% CI, 1.21-3.62) and multivariate analysis after adjustment for age, sex, race and type of pulmonary hypertension (adjusted HR=2.48 per tertile; 95% CI, 1.33-4.6), according to data presented.

“Galectin-3 is being studied as a therapeutic target in HF and perhaps should be similarly investigated in [pulmonary hypertension],” Mannem said. “In the future, galectin-3 values can help us guide and treat PAH and [HF with preserved ejection fraction-induced pulmonary hypertension] patients more aggressively if their galectin-3 is significantly elevated.”

The researchers said further studies are needed to confirm these data and to investigate the underlying mechanisms of galectin-3. – by Erik Swain

These data detailing the observation that higher levels of galectin-3 in pulmonary hypertension patients is associated with higher mortality is interesting and, arguably, sets up a target for therapies in the future. Before this is likely to be accomplished, however, we need a greater understanding of what elevated galectin-3 levels mean in this clinical situation. Is it simply a passive bystander not intimately related to the pathophysiology of clinical deterioration in pulmonary hypertension patients or does the molecule have a specific role in the process? Clearly, more studies addressing these questions in large cohorts of patients need to be done. The observation is, indeed, interesting.

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